A comparative genome-wide study of ncRNAs in trypanosomatids

<p>Abstract</p> <p>Background</p> <p>Recent studies have provided extensive evidence for multitudes of non-coding RNA (ncRNA) transcripts in a wide range of eukaryotic genomes. ncRNAs are emerging as key players in multiple layers of cellular regulation. With the availability of many whole genome sequences, comparative analysis has become a powerful tool to identify ncRNA molecules. In this study, we performed a systematic genome-wide in silico screen to search for novel small ncRNAs in the genome of <it>Trypanosoma brucei </it>using techniques of comparative genomics.</p> <p>Results</p> <p>In this study, we identified by comparative genomics, and validated by experimental analysis several novel ncRNAs that are conserved across multiple trypanosomatid genomes. When tested on known ncRNAs, our procedure was capable of finding almost half of the known repertoire through homology over six genomes, and about two-thirds of the known sequences were found in at least four genomes. After filtering, 72 conserved unannotated sequences in at least four genomes were found, 29 of which, ranging in size from 30 to 392 nts, were conserved in all six genomes. Fifty of the 72 candidates in the final set were chosen for experimental validation. Eighteen of the 50 (36%) were shown to be expressed, and for 11 of them a distinct expression product was detected, suggesting that they are short ncRNAs. Using functional experimental assays, five of the candidates were shown to be novel H/ACA and C/D snoRNAs; these included three sequences that appear as singletons in the genome, unlike previously identified snoRNA molecules that are found in clusters. The other candidates appear to be novel ncRNA molecules, and their function is, as yet, unknown.</p> <p>Conclusions</p> <p>Using comparative genomic techniques, we predicted 72 sequences as ncRNA candidates in <it>T. brucei</it>. The expression of 50 candidates was tested in laboratory experiments. This resulted in the discovery of 11 novel short ncRNAs in procyclic stage <it>T. brucei</it>, which have homologues in the other trypansomatids. A few of these molecules are snoRNAs, but most of them are novel ncRNA molecules. Based on this study, our analysis suggests that the total number of ncRNAs in trypanosomatids is in the range of several hundred.</p

International recommendations for glucose control in adult non diabetic critically ill patients

The purpose of this research is to provide recommendations for the management of glycemic control in critically ill patients.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishedPour la Société Française d'Anesthésie-Réanimation (SFAR); Société de Réanimation de langue Française (SRLF) and the Experts grou

The evolution and storage of primitive melts in the Eastern Volcanic Zone of Iceland: the 10 ka Grímsvötn tephra series (i.e. the Saksunarvatn ash)

Major, trace and volatile elements were measured in a suite of primitive macrocrysts and melt inclusions from the thickest layer of the 10 ka Grímsvötn tephra series (i.e. Saksunarvatn ash) at Lake Hvítárvatn in central Iceland. In the absence of primitive tholeiitic eruptions (MgO > 7 wt.%) within the Eastern Volcanic Zone (EVZ) of Iceland, these crystal and inclusion compositions provide an important insight into magmatic processes in this volcanically productive region. Matrix glass compositions show strong similarities with glass compositions from the AD 1783–84 Laki eruption, confirming the affinity of the tephra series with the Grímsvötn volcanic system. Macrocrysts can be divided into a primitive assemblage of zoned macrocryst cores (An_78–An_92, Mg#_cpx = 82–87, Fo_79.5–Fo_87) and an evolved assemblage consisting of unzoned macrocrysts and the rims of zoned macrocrysts (An_60–An_68, Mg#_cpx = 71–78, Fo_70–Fo_76). Although the evolved assemblage is close to being in equilibrium with the matrix glass, trace element disequilibrium between primitive and evolved assemblages indicates that they were derived from different distributions of mantle melt compositions. Juxtaposition of disequilibrium assemblages probably occurred during disaggregation of incompatible trace element-depleted mushes (mean La/Yb_melt = 2.1) into aphyric and incompatible trace element-enriched liquids (La/Yb_melt = 3.6) shortly before the growth of the evolved macrocryst assemblage. Post-entrapment modification of plagioclase-hosted melt inclusions has been minimal and high-Mg# inclusions record differentiation and mixing of compositionally variable mantle melts that are amongst the most primitive liquids known from the EVZ. Coupled high field strength element (HFSE) depletion and incompatible trace element enrichment in a subset of primitive plagioclase-hosted melt inclusions can be accounted for by inclusion formation following plagioclase dissolution driven by interaction with plagioclase-undersaturated melts. Thermobarometric calculations indicate that final crystal-melt equilibration within the evolved assemblage occurred at ~1140°C and 0.0–1.5 kbar. Considering the large volume of the erupted tephra and textural evidence for rapid crystallisation of the evolved assemblage, 0.0–1.5 kbar is considered unlikely to represent a pressure of long-term magma accumulation and storage. Multiple thermometers indicate that the primitive assemblage crystallised at high temperatures of 1240–1300°C. Different barometers, however, return markedly different crystallisation depth estimates. Raw clinopyroxene-melt pressures of 5.5–7.5 kbar conflict with apparent melt inclusion entrapment pressures of 1.4 kbar. After applying a correction derived from published experimental data, clinopyroxene-melt equilibria return mid-crustal pressures of 4±1.5 kbar, which are consistent with pressures estimated from the major element content of primitive melt inclusions. Long-term storage of primitive magmas in the mid-crust implies that low CO_2 concentrations measured in primitive plagioclase-hosted inclusions (262–800 ppm) result from post-entrapment CO_2 loss during transport through the shallow crust. In order to reconstruct basaltic plumbing system geometries from petrological data with greater confidence, mineral-melt equilibrium models require refinement at pressures of magma storage in Iceland. Further basalt phase equilibria experiments are thus needed within the crucial 1–7 kbar range.D.A.N. was supported by a Natural Environment Research Council studentship (NE/1528277/1) at the start of this project. SIMS analyses were supported by Natural Environment Research Council Ion Microprobe Facility award (IMF508/1013).This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00410-015-1170-

Vision Quality of Life with Time Survey: Normative Data and Repeatability

Michaela E Dungan,1 Mitchell Scheiman,2 Chang Yaramothu1,3 1School of Applied Engineering and Technology, New Jersey Institute of Technology, Newark, NJ, USA; 2Pennsylvania College of Optometry, Salus University, Philadelphia, PA, USA; 3Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USACorrespondence: Chang Yaramothu, School of Applied Engineering and Technology, New Jersey Institute of Technology, University Heights, Newark, NJ, 07102, USA, Tel +1 973642-4844, Email [email protected]: To develop a novel Vision Quality of Life (QoL) survey that emphasizes the amount of time a visual activity can be performed before symptoms occur.Methods: The Vision Quality of Life with Time (VisQuaL-T) survey was developed with 10 daily activities and a list of common visual symptoms. Participants were recruited from a university campus. Participants were not excluded based on binocular impairments to obtain a normative dataset. Participants were instructed to denote when they first experience symptoms within certain time ranges. If participants did not engage in one of the 10 activities, they were instructed to denote “N/A”. A composite score (range 0– 3) was determined by only accounting for the questions that were answered.Results: The normative data cohort had a sample size of 376 participants and the repeatability cohort had 54 participants. The normative, test, and retest datasets had a mean composite score of 2.47± 0.54, 2.69± 0.42, and 2.67± 0.49 and 95% confidence interval of 2.38– 2.71, 2.58– 2.81, 2.54– 2.80, respectively. There was good reliability and high correlation between the test and retest timepoints with an ICC of 0.825 and a Pearson correlation coefficient of 0.839 in the repeatability cohort. The normative data cohort showed good internal consistency with a Cronbach’s alpha value of 0.803. Test and retest timepoints showed no statistical significance among the individual questions (p > 0.1).Conclusion: A lower bound score of 2.4 can potentially be used to differentiate visually normal and symptomatic participants. Statistical analysis showed the survey is repeatable and reliable. Using time as a metric for assessing symptomology could be a useful method for identifying patients with QoL issues and for assessing effectiveness of binocular vision, accommodative, and eye movement treatments.Keywords: quality of life, timed survey, endurance, visual symptoms, patient-reported outcome measur